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A qualitative exploration of GPs’ perspectives on managing chronic nonspecific musculoskeletal pain in Australian general practice – a focus group study
Get PDFCreative Commons Attribution-NonCommercial 4.0 International LicenseObjective: Chronic nonspecific musculoskeletal pain (CNMP) is a complex idiopathic condition that causes significant disruption to patients’ lives, their relationships, and functionality. The cause of CNMP is not fully understood, which makes diagnosis and management challenging. As general practitioners (GPs) are central to the management of chronic pain, their perspectives on managing CNMP are important.
Purpose: To explore the clinical reasoning GPs use when diagnosing and managing CNMP.
Methods: A qualitative study design using focus group discussion was conducted with Australian GPs. Five focus group discussion were conducted across Adelaide. All focus group discussions were audio-recorded, and transcripts were coded and analyzed thematically with the program NVivo.
Results: The main themes remained consistent across the five focus group discussion’s: the ambiguous cause of CNMP; sex differences; developing the “right strategy”; patient-centered care; and verifying vitamin D levels.
Conclusion: The findings show that GPs use a patient-centered approach tailored to individual patients’ medical history, physical examination findings, and psychosocial health. There was general concern about low levels of vitamin D in patients with CNMP, and vitamin D supplements were recommended if indicated by a patient’s history
Mean transit times in headwater catchments: insights from the Otway Ranges, Australia
Get PDFThis work is distributed under the Creative Commons Attribution 3.0 License.Understanding the timescales of water flow through catchments and the sources of stream water at different flow conditions is critical for understanding catchment behaviour and managing water resources. Here, tritium (3H) activities, major ion geochemistry and streamflow data were used in conjunction with lumped parameter models (LPMs) to investigate mean transit times (MTTs) and the stores of water in six headwater catchments in the Otway Ranges of southeastern Australia. 3H activities of stream water ranged from 0.20 to 2.14 TU, which are significantly lower than the annual average 3H activity of modern local rainfall, which is between 2.4 and 3.2 TU. The 3H activities of the stream water are lowest during low summer flows and increase with increasing streamflow. The concentrations of most major ions vary little with streamflow, which together with the low 3H activities imply that there is no significant direct input of recent rainfall at the streamflows sampled in this study. Instead, shallow younger water stores in the soils and regolith are most likely mobilised during the wetter months.
MTTs vary from approximately 7 to 230 years. Despite uncertainties of several years in the MTTs that arise from having to assume an appropriate LPM, macroscopic mixing, and uncertainties in the 3H activities of rainfall, the conclusion that they range from years to decades is robust. Additionally, the relative differences in MTTs at different streamflows in the same catchment are estimated with more certainty. The MTTs in these and similar headwater catchments in southeastern Australia are longer than in many catchments globally. These differences may reflect the relatively low rainfall and high evapotranspiration rates in southeastern Australia compared with headwater catchments elsewhere.
The long MTTs imply that there is a long-lived store of water in these catchments that can sustain the streams over drought periods lasting several years. However, the catchments are likely to be vulnerable to decadal changes in land use or climate. Additionally, there may be considerable delay in contaminants reaching the stream. An increase in nitrate and sulfate concentrations in several catchments at high streamflows may represent the input of contaminants through the shallow groundwater that contributes to streamflow during the wetter months. Poor correlations between 3H activities and catchment area, drainage density, land use, and average slope imply that the MTTs are not controlled by a single parameter but a variety of factors, including catchment geomorphology and the hydraulic properties of the soils and aquifers
Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe–gut–brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography–mass spectrometry, nuclear magnetic resonance, and liquid chromatography–mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about “depression microbes” impacting on liver metabolism
Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review
Get PDFThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background
The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.
Objectives
The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.
Methods
A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.
Results
The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.
Conclusions
There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching
A literature scoping review of eating practices and food environments in 1 and 2-person households in the UK, Australia and USA
Get PDF© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyThe purpose of this article is to map the data currently available on the subject of eating practices and food environments in small (i.e. one- and two-person) households. Specifically, the enquiry is focused on commensality; the act of eating together. Research dates from the late 1980s, however, there are few recent publications on this subject. Searching Ovid MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, ProQuest and Google Scholar, 2949 papers were found, but only 457 discussed any element of the research questions. These were further distilled to a count of 117, by abstract reading to 53 at which point, quality, location and study focus eliminated a further 34 articles leaving 19 articles. After full reading, it was clear that only seven of these focused on the research question in detail and these are marked as four-star articles by bold text. The 19 articles are analysed for quality and their aspects of relevance to the central research question is discussed
Surgical site infection in overweight and obese Total Knee Arthroplasty patients
Get PDF© 2018 Prof. PK Surendran Memorial Education Foundation. Published by Elsevier, a division of RELX India, Pvt. Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyPurpose
This aim of this study was to evaluate the rate of surgical site infection (SSI) in patients undergoing Total Knee Arthroplasty (TKA), to improve our understanding of the associations between infection rate and obesity.
Methods
Data was reviewed for 839 primary TKA procedures performed at a National Arthroplasty Centre over one year (April 2007–March 2008). SSI data was collected at 30 days and one year post-operatively. Patients were grouped guided by the WHO classifications of obesity; normal (BMI < 25.0), overweight (BMI 25.00–29.99), obese class I (BMI 30.00–34.99), obese class II (BMI 35.00–39.99), obese class III (BMI ≥ 40.00). Statistical significance was assessed by Fisher’s Exact Test.
Results
When grouped by BMI, 30.9% of patients were obese class I, 19.0% obese class II and 8.7% obese class III. Of the total cohort, 22 patients (2.6%) had superficial SSI and 13 (1.5%) had deep SSI. When comparing the obese class III cohort to all other cohorts (non-obese class III), the odds ratios for superficial SSI was 4.20 (95% CI [1.59, 11.09]; p = 0.009) and deep SSI was 6.97 (95% CI [2.22, 21.89]; p = 0.003). In the obese class III cohort, superficial SSI rate was higher in females (8.9%) than males (5.9%), yet deep SSI demonstrated the opposite, with a higher occurrence in males (11.8%) compared to females (5.4%).
Conclusion
This study suggests that obese class III TKA patients are at increased odds of superficial and deep SSI compared to other BMI cohorts. Interestingly, male obese class III patients demonstrated a higher rate of deep infection compared to their female counterparts. However, it must be noted that study findings are limited as confounders were unable to be accounted for in this retrospective study design
Semianalytical solutions for contaminant transport under variable velocity field in a coastal aquifer
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyExisting closed-form solutions of contaminant transport problems are limited by the mathematically convenient assumption of uniform flow. These solutions cannot be used to investigate contaminant transport in coastal aquifers where seawater intrusion induces a variable velocity field. An adaptation of the Fourier-Galerkin method is introduced to obtain semi-analytical solutions for contaminant transport in a confined coastal aquifer in which the saltwater wedge is in equilibrium with a freshwater discharge flow. Two scenarios dealing with contaminant leakage from the aquifer top surface and contaminant migration from a source at the landward boundary are considered. Robust implementation of the Fourier-Galerkin method is developed to efficiently solve the coupled flow, salt and contaminant transport equations. Various illustrative examples are generated and the semi-analytical solutions are compared against an in-house numerical code. The Fourier series are used to evaluate relevant metrics characterizing contaminant transport such as the discharge flux to the sea, amount of contaminant persisting in the groundwater and solute flux from the source. These metrics represent quantitative data for numerical code validation and are relevant to understand the effect of seawater intrusion on contaminant transport. It is observed that, for the surface contamination scenario, seawater intrusion limits the spread of the contaminant but intensifies the contaminant discharge to the sea. For the landward contamination scenario, moderate seawater intrusion affects only the spatial distribution of the contaminant plume while extreme seawater intrusion can increase the contaminant discharge to the sea. The developed semi-analytical solution presents an efficient tool for the verification of numerical models. It provides a clear interpretation of the contaminant transport processes in coastal aquifers subject to seawater intrusion. For practical usage in further studies, the full open source semi-analytical codes are made available at the website https://lhyges.unistra.fr/FAHS-Marwan
High-performance all-polymer solar cells based on fluorinated naphthalene diimide acceptor polymers with fine-tuned crystallinity and enhanced dielectric constants
Get PDF© 2018 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (Jan 2018) in accordance with the publisher’s archiving policyGrowing interests have been devoted to the synthesis of polymer acceptors as alternatives to fullerene derivatives to realize high-performance and stable all-polymer solar cells (all-PSCs). So far, one of the key factors that limit the performance of all-PSCs is low photocurrent density (normally < 14 mA/cm2). One potential solution is to improve the dielectric constants (εr) of polymer:polymer blends, which tend to reduce the binding energy of excitons, thus boosting the exciton dissociation efficiencies. Nevertheless, the correlation between εr and photovoltaic performance has been rarely investigated for all-PSCs. In this work, five fluorinated naphthalene diimide (NDI)-based acceptor polymers, with different content of fluorine were synthesized. The incorporation of fluorine increased the εr of the acceptor polymers and blend films, which improved the charge generation and overall photocurrent of the all-PSCs. As a result, the PTB7-Th:PNDI-FT10 all-PSC attained a high power conversion efficiency (PCE) of 7.3% with a photocurrent density of 14.7 mA/cm2, which surpassed the values reported for the all-PSC based on the non-fluorinated acceptor PNDI-T10. Interestingly, similarly high photovoltaic performance was maintained regardless of a large variation of donor:acceptor ratios, which revealed the good morphological tolerance and the potential for robust production capability of all-PSCs
Co‐expression of μ and ∂ opioid receptors by mouse colonic nociceptors
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Copyright © 2018 The British Pharmacological Society All rights reserved.
This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyBackground and Purpose
To better understand opioid signaling in visceral nociceptors, we examined the expression and selective activation of mu (MOR) and delta opioid receptors (DOR) by dorsal root ganglia (DRG) neurons innervating the mouse colon.
Experimental Approach
DRG neurons projecting to the colon were identified by retrograde tracing. DOR‐GFP reporter mice, in situ hybridization, single‐cell RT‐PCR, and MOR‐specific antibodies were used to characterize expression of MOR and DOR. Voltage‐gated Ca2+ currents and neuronal excitability were recorded in small diameter nociceptive neurons (capacitance < 30pF) by patch clamp and ex vivo single‐unit afferent recordings were obtained from the colon.
Key Results
In situ hybridization of oprm1 expression in Fast Blue‐labeled DRG neurons was observed in 61% of neurons. MOR and DOR were expressed by 36‐46% of colon DRG neurons, and co‐expressed by ~25 % of neurons. MOR and DOR agonists inhibited Ca2+ currents in DRG and these effects were blocked by opioid antagonists. One or both agonists inhibited action potential firing by colonic afferent endings. Incubation of neurons with supernatants from inflamed colon segments inhibited Ca2+ currents and neuronal excitability. The MOR but not the DOR antagonist, inhibited the supernatant effects on Ca2+ currents, whereas both antagonists inhibited their actions on neuronal excitability.
Conclusions and Implications
A significant number of small diameter colonic nociceptors co‐express MOR and DOR and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at MOR or DOR or their heterodimers may be effective in the treatment of visceral pain
Low-frequency and rare variants may contribute to elucidate the genetics of major depressive disorder
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Major depressive disorder (MDD) is a common but serious psychiatric disorder with significant levels of morbidity and mortality. Recent genome-wide association studies (GWAS) on common variants increase our understanding of MDD; however, the underlying genetic basis remains largely unknown. Many studies have been proposed to explore the genetics of complex diseases from a viewpoint of the “missing heritability” by considering low-frequency and rare variants, copy-number variations, and other types of genetic variants. Here we developed a novel computational and statistical strategy to investigate the “missing heritability” of MDD. We applied Hamming distance on common, low-frequency, and rare single-nucleotide polymorphism (SNP) sets to measure genetic distance between two individuals, and then built the multi-dimensional scaling (MDS) pictures. Whole-exome genotyping data from a Los Angeles Mexican-American cohort (203 MDD and 196 controls) and a European-ancestry cohort (473 MDD and 497 controls) were examined using our proposed methodology. MDS plots showed very significant separations between MDD cases and healthy controls for low-frequency SNP set (P value < 2.2e−16) and rare SNP set (P value = 7.681e−12). Our results suggested that low-frequency and rare variants may play more significant roles in the genetics of MDD